Duchenne's Muscular Dystrophy (DMD) is a genetic disease that results from a variety of different mutations in the gene coding for dystrophin. Dystrophin is a large cytoskeletal protein that provides structural integrity to contracting muscle fibers. DMD patients produce little, if any, functional dystrophin, resulting in fragility of the sarcolemmal membranes that surround each muscle fiber. As a consequence of this fragility, DMD patients exhibit progressive degeneration of skeletal and cardiac muscles, with onset typically at age two to six. The disease causes generalized weakness and muscle wasting. Survival is rare beyond the early 30s.
In a related and somewhat milder condition, Becker muscular dystrophy (BMD), the patient produces some functional dystrophin, but not enough to provide normal durability and maintenance of muscle tissue. BMD patients usually have a longer lifespan than DMD patients.
While DMD and BMD are presently incurable diseases, one therapeutic approach under investigation involves treatment with agents that increase the levels of a protein called utrophin. Utrophin is structurally and functionally similar to dystrophin. Moreover, utrophin is normally present in muscle fibers during fetal development and remains in the mature fibers at neuromuscular junctions. At sufficient levels and with appropriate localization to the sarcolemma, utrophin shows evidence of partially compensating for the absence of dystrophin in animal models of DMD.
DMD and BMD patients have a normal utrophin gene, and it may be possible to increase the strength of muscle fibers in patients by increasing utrophin production.
Thus, there is a need for agents that increase utrophin production and/or sarcolemmal localization of utrophin.